Chemokine production by rat alveolar macrophages is inhibited by taurine chloramine
Chemokine production by rat alveolar macrophages is inhibited by taurine chloramine
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DOI：
10.1016/s0165-2478(01)00291-7
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发表时间：
2002-01-01
影响因子：
4.4
通讯作者：
Quinn, MR
中科院分区：
文献类型：
--
作者：
Liu, Y;Quinn, MR
在多种以炎症为致病特征的模型中，牛磺酸可保护肺组织免受氧化剂引起的损伤。牛磺酸的保护机制被认为与牛磺酸氯胺 (Tau-Cl) 的形成和随后的作用有关，Tau-Cl 是由与中性粒细胞相关的卤化物依赖性髓过氧化物酶系统的活性产生的。由于趋化因子是由活化的肺泡巨噬细胞分泌的，并且主要参与肺部炎症反应的传播，因此我们确定了 Tau-Cl 对 NR8383（一种源自大鼠肺泡巨噬细胞的克隆细胞系）中 MCP-1 和 MIP-2 产生的影响。用LPS和IFN-γ激活NR8383细胞导致MCP-1和MIP-2在接下来的24小时内在条件培养基中积累，并且这被Tau-Cl以浓度依赖性方式抑制。 MCP-1 和 MIP-2 mRNA 表达的 Northern 印迹分析揭示了 Tau-Cl 的浓度依赖性抑制。相对于 MIP-2，Tau-Cl 更有效地抑制 MCP-1 转录物的表达。由于这些趋化因子基因的启动子区域受 NF-kappaB 调节，因此评估核蛋白提取物中 NF-kappaB 与其序列特异性识别位点 (EMSA) 的结合情况。相对于活化的对照细胞，Tau-Cl处理的细胞表达的核NF-κB结合减少。 NF-kappaB 二聚体的组成主要包含 p50 和 p65 亚基，但也存在一些 c-Rel。这些结果表明，Tau-Cl 通过部分涉及 NF-kappaB 信号通路的机制抑制激活的 NR8383 细胞产生趋化因子。 (C) 2002 Elsevier Science B.V. 保留所有权利。
Taurine protects lung tissue from oxidant-induced damage in a variety of models that involve inflammation as a pathogenic feature. The mechanism of taurine protection is thought to be related to the formation and subsequent action of taurine chloramine (Tau-Cl), Tau-Cl results from the activity of a halide-dependent myeloperoxidase system associated with neutrophils. Since chemokines are secreted by activated alveolar macrophages and are prominently involved in propagating the inflammatory response in lung, we determined the effects of Tau-Cl on MCP-1 and MIP-2 production in NR8383, a cloned cell line derived from rat alveolar macrophages. Activation of NR8383 cells with LPS and lFN-gamma resulted in accumulation of MCP-1 and MIP-2 in the conditioned media over the following 24-h and this was inhibited by Tau-Cl in a concentration dependent fashion. Northern blot analyses of MCP-1 and MIP-2 rnRNA expression revealed concentration dependent inhibition by Tau-Cl. Expression of MCP-1 transcripts was more potently inhibited by Tau-Cl relative to that of MIP-2. Since the promoter regions of these chemokine genes are regulated by NF-kappaB, nuclear protein extracts were evaluated for NF-kappaB binding to its sequence specific recognition site (EMSA). Tau-Cl treated cells expressed reduced nuclear NF-kappaB binding relative to the activated control cells. The composition of the NF-kappaB dimer contained predominately p50 and p65 subunits, but some c-Rel was also present. These results suggest that Tau-Cl inhibits production of chemokines by activated NR8383 cells through a mechanism that involves, in part, the NF-kappaB signaling pathway. (C) 2002 Elsevier Science B.V. All rights reserved.